Figure 8.

ROCK-Myosin II Inhibition Improves Efficacy of Immune Checkpoint Inhibitors

(A) Top, schematic of treatment. Bottom, growth of 5555 allografts in C57BL/6J mice after treatment. Pooled data from 3 experiments (n = 6–8 mice/group/experiment).

(B–D) Images and quantification of p-MLC2 (B), CD206⁺ (C), and FOXP3⁺ (D) cells in 5555 tumors at endpoint (pooled data from 2 experiments). Ratio CD206⁺/F4/80⁺ shown. Scale bars, 100 μm (p-MLC2, CD206) and 50 μm (FOXP3).

(E) Schematic of experiment.

(F) Left, growth of 5555 allografts after treatment. Right, quantification of p-MLC2, CD206⁺, F4/80⁺, and ratio CD206⁺/F4/80⁺ in anti-PD-1/NR or Resp tumors.

(G) Left, growth of 5555 anti-PD-1/NR allografts in new recipient mice after treatment (n = 7-8 mice/group). Right, survival plot.

(H) Images and quantification of p-MLC2 and PD-L1 on tumor cells in tumors from (G). Scale bars, 25 μm.

(I) Left, images and quantification of PD-L1 on CD206⁺ cells in tumors from (G). Images show merged pseudo-colors for each staining. Scale bar, 50 μm. Right, quantification of FOXP3⁺ Tregs in tumors from (G).

(A–D and G–I) ROCKi GSK269962A.

Boxplots show median (center line); interquartile range (box); min-max (whiskers); and individual mice (circles). p values by ANOVA with Benjamini, Krieger, and Yekutieli correction (B–D and H–I), t test (F), chi-square test: percentage regressions in (A) and (G). ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001; n.s., not significant. See also Figure S8.